Translocation of bacterial LPS is associated with self-reported cognitive abilities in men living with HIV receiving antiretroviral therapy

Abstract

Background Gut damage allows translocation of bacterial lipopolysaccharide (LPS) and fungal β-D-glucan (BDG) into the blood. This microbial translocation contributes to systemic inflammation and risk of non-AIDS comorbidities in people living with HIV, including those receiving antiretroviral therapy (ART). We assessed whether markers of gut damage and microbial translocation were associated with cognition in ART-treated PLWH. Methods Eighty ART-treated men living with HIV from the Positive Brain Health Now Canadian cohort were included. Brief cognitive ability measure (B-CAM) and 20-item patient deficit questionnaire (PDQ) were administered to all participants. Three groups were selected based on their B-CAM levels. We excluded participants who received proton pump inhibitors or antiacids in the past 3 months. Cannabis users were also excluded. Plasma levels of intestinal fatty acid binding protein (I-FABP), regenerating islet-derived protein 3 α (REG3α), and lipopolysaccharides (LPS = were quantified by ELISA, while 1–3-β-D-glucan BDG) levels were assessed using the Fungitell assay. Univariable, multivariable, and splines analyses were performed. Results Plasma levels of I-FABP, REG3α, LPS and BDG were not different between groups of low, intermediate and high B-CAM levels. However, LPS and REG3α levels were higher in participants with PDQ higher than the median. Multivariable analyses showed that LPS association with PDQ, but not B-CAM, was independent of age and level of education. I-FABP, REG3α, and BDG levels were not associated with B-CAM nor PDQ levels in multivariable analyses. Conclusion In this well characterized cohort of ART-treated men living with HIV, bacterial but not fungal translocation was associated with presence of cognitive difficulties. These results need replication in larger samples.

Human Immunodeficiency Virus as a Risk Factor for Cardiovascular Disease

“…The depletion of these cells leads to an imbalance of the Th17/Treg ratio and enhanced production of cytokines, including IL-6, IL-17, IL-1β, IL-12, and IL-4, which disrupts epithelial junctions in the gastrointestinal mucosal barrier and therefore leads to increased microbial translocation [ 49 , 50 ]. There are known markers of microbial translocation, including plasma levels of lipopolysaccharide and soluble CD14, which are bacterial products, and (1➔3)-β-D-Glucan, a fungal product, that are elevated in untreated PLWH [ 51 , 52 ]. In addition to Th17 CD4 + lymphocytes, the decrease of mucosal-associated invariant T cells (MAIT) induced by chronic inflammation may contribute to increased susceptibility to microbial translocation.…”

The Influence of Oral Terbinafine on Gut Fungal Microbiome Composition and Microbial Translocation in People Living with HIV Treated for Onychomycosis

“…Convergent evidence indicates that PLWH display an altered composition of their intestinal microbiota and their by-products, a concept referred to as dysbiosis [2,3]. Gut barrier dysfunction (leaky gut) and the translocation of microbial products (endotoxins) into the systemic circulation have been linked with dysbiosis and non-AIDS comorbidities like cardiovascular disease, alterations of neurocognition, and cancer [1,[4][5][6][7][8][9]. We have showed that the elevated plasma levels of beta-D-glucan, a byproduct of fungi released from the gut into the circulating blood, were an LPS-independent contributor to inflammation in PLWH [10].…”